Giraldo Gustavo Adolfo, Ayala-Ramírez Paola, Prieto Juan Carlos, García-Robles Reggie, Acosta Johanna Carolina
Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.
Instituto de Investigación en Nutrición, Genética y Metabolismo, Universidad El Bosque, Bogotá, Colombia.
Meta Gene. 2015 Dec 23;7:83-9. doi: 10.1016/j.mgene.2015.12.004. eCollection 2016 Feb.
Maroteaux-Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is an autosomal recessive lysosomal storage disease caused by a deficient activity of the enzyme arylsulfatase B (ARSB), required to degrade dermatan sulfate. The onset and progression of the disease vary, producing a spectrum of clinical presentation. So far, 133 mutations have been reported. The aim of this study is to determine the mutations in the ARSB gene that are responsible for this disease in Colombian patients.
Fourteen patients with clinical manifestations and biochemical diagnosis of MPS VI were studied, including two siblings. The 8 exons of the gene were directly sequenced from patients' DNA, and 14 mutations were found. 57% of these mutations had not been previously reported (p.H111P, p.C121R, p.G446S, p.534W, p.S334I, p.H147P, c.900T > G, and c.1531_1553del) and 43% had been previously reported (p.G144R, p.W322, p.G302R, p.C447F, p.L128del, and c.1143-1G > C). Of the previously reported mutations, 80% have been associated with severe phenotypes and 20% with intermediate-severe phenotypes. Bioinformatic predictions indicate that the new mutations reported in this paper are also highly deleterious.
Most of the Colombian patients in this study had private mutations.
马罗-拉米综合征，即黏多糖贮积症（MPS）VI型，是一种常染色体隐性溶酶体贮积病，由降解硫酸皮肤素所需的芳基硫酸酯酶B（ARSB）活性不足引起。该疾病的发病和进展各不相同，呈现出一系列临床表现。到目前为止，已报道了133种突变。本研究的目的是确定哥伦比亚患者中导致该疾病的ARSB基因突变。
对14例有MPS VI临床表现和生化诊断的患者进行了研究，包括一对兄妹。从患者DNA中直接对该基因的8个外显子进行测序，发现了14种突变。这些突变中有57%此前未被报道（p.H111P、p.C121R、p.G446S、p.534W、p.S334I p.H147P、c.900T>G和c.1531_1553del），43%此前已被报道（p.G144R、p.W322、p.G302R、p.C447F、p.L128del和c.1143-1G>C）。在先前报道的突变中，80%与严重表型相关，20%与中度-严重表型相关。生物信息学预测表明，本文报道的新突变也具有高度有害性。
本研究中的大多数哥伦比亚患者有私人突变。
